New thoughts on migraine pain

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Johns Hopkins researchers think they've found the source of pain in migraines. It is not the blood vessels inside the brain that are causing the severe distress, they say, but changes in the tissues that envelop the brain. The results, presented at this week's American Academy of Neurology meeting in Toronto, may contribute to a better understanding of this largely enigmatic affliction.

Patients in the study came to Johns Hopkins in the midst of a well-documented migraine attack and pinpointed the site of their headache on a diagram. They then received an IV injection of the common blood plasma protein, albumen, tagged with a radioactive isotope.As a baseline, radiologists took SPECT (single photon emission computerized tomography) scans of the head at 10 minutes and 3 hours, and then again several days later after headaches subsided. During inflammation that occurs during a migraine, blood vessels in the meninges became unusually permeable to molecules such as albumen. The SPECT scans then picked up the albumen leakage into surrounding tissues. The images showed bright, diffuse patches -- a sign of inflammation -- at areas in the meninges that precisely matched places where patients said they felt their headaches, thus linking abnormalities in the meninges with the pain.

But the inflammation itself isn't the immediate cause of migraine pain. The researchers believe that comes from abnormal nerve activity. Animal studies elsewhere show that electrically stimulating the trigeminal nerve, the major nerve leading from the brain to head and face, inflames the meninges. Unlike inflammation sparked by trauma or infection, this neurogenic inflammation" originates from chemicals -- neuropeptides --released by nerve endings. Neuropeptides trigger inflammation,"said team leader Marco Pappagallo, but they also sensitize nearby pain receptors in the meninges which send the message of pain."

The major drugs for migraines -- ergot-based ones or sumatriptan, work because they block release of neuropeptides -- a further bit of evidence, he says. Traditional ideas on the origin of the pain looked at changes in blood flow to the head, particularly the scalp. But Pappagallo has long suspected abnormalities in the meninges. For one thing," he adds, the symptoms of a bad migraine headache are the same as in meningitis, the bacterial or viral inflammation of the meninges: throbbing headache, nausea, and sensitivity to light and sound." While the work is a very small pilot study, the SPECTimages undeniably link the site of pain with the meninges, Pappagallo says. There's no other way to explain something like this."